A wide variety of drugs has been targeted as antitumor agents. They are roughly classified into alkylating agents, platinum-based compounds, antimetabolites, topoisomerase inhibitors, microtubule inhibitors, antitumor antibiotics, molecular target drugs, and the like. Further, in recent years, the combined use of multiple drugs, instead of the administration of a single antitumor agent, has been widely prevalent.
AKT is a serine/threonine-specific kinase serving as a downstream effector of phosphatidylinositol-3 kinase (PI3 kinase), which is activated by a receptor tyrosine kinase signal. AKT is frequently activated or highly expressed in many cancers (renal cell cancer, stomach cancer, breast cancer, lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, hepatic cell cancer, multiple myeloma, lymphoma, leukemia, head and neck cancer, melanoma, and the like), and genetic amplification or activating mutation has been reported in some cancers (NPD 1). As for the function, AKT is reported to play an important role in tumorigenesis such as cell proliferation, apoptosis resistance, angiogenesis, metastasis and invasion, as well as glucose metabolism and lipid metabolism (NPD 2). AKT is also reported to be highly expressed in tumors unresponsive or resistant to existing treatments using antitumor agents. Thus, there has been an expectation regarding the effect of the combined use of an AKT inhibitor and existing antitumor agents, including molecular-targeted antitumor agents (NPD 3).
For example, there are reports of treatments using a combination of MK-2206, which is an AKT inhibitor, and docetaxel (NPD 4 and PTD 1).